Abstract
BackgroundClinically relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need.MethodsWe analyzed tumor vascular density and VEGFR2 protein expression in various subsets of primary human BRCs (186 females; Mean age: 59 years; range 33–88 years), using a tissue microarray. Discrete VEGFR2+ and CD34+ tumor vessels were manually scored in invasive ductal, lobular, mixed ductal-lobular and colloid (N = 139, 22, 18, 7) BRC cores.ResultsThe observed CD34+ and VEGFR2+ tumor vascular counts in individual cases were heterogeneous. Mean CD34+ and VEGFR2+ tumor vessel counts were 11 and 3.4 per tumor TMA core respectively. Eighty-nine of 186 (48%) cases had >10 CD34+ tumor vessels, while 97/186 (52%) had fewer CD34+ vessels in each TMA core. Of 169 analyzable cores in the VEGFR2 stained TMA, 90 (53%) showed 1–5 VEGFR2+ tumor vessels/TMA core, while 42/169 (25%) cores had no detectable VEGFR2+ tumor vessels. Thirteen of 169 (8%) cases also showed tumor cell (cytoplasmic/membrane) expression of VEGFR2. Triple-negative breast cancers (TNBCs) appeared to be less vascular (Mean VD = 9.8, range 0–34) than other breast cancer subtypes. Overall, VEGFR2+ tumor vessel counts were significantly higher in HER2+ as compared to HR+ (p = 0.04) and TNBC (p = 0.02) tissues. Compared to HER2− cases, HER2+ breast cancers had higher VEGFR2+ tumor vessel counts (p = 0.007).ConclusionCharacterization of pathologic angiogenesis in HER2+ breast cancer provides scientific rationale for future investigation of clinical activity of agents targeting the VEGF/VEGFR2 axis in this clinically aggressive breast cancer subtype.
Highlights
Relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need
89 of 186 evaluable tissue microarray (TMA) cores exhibited more than 10 CD34+ vessels/core, while only 8 of 169 evaluable TMA cores had more than 10 vascular endothelial growth factor receptor 2 (VEGFR2)+ vessels/core (Table 2), implying that only a proportion of CD34+ tumor stromal vessels co-expressed VEGFR2 protein in their endothelial lining
Of 164 breast cancer cases including all histologic types, 127 (77.4%) had a few (
Summary
Relevant predictive biomarkers to tailor anti-angiogenic therapies to breast cancer (BRC) patient subpopulations are an unmet need. Breast cancer is a heterogeneous disease with distinct histopathologic, epidemiologic, clinical, biologic and molecular characteristics. Compared to other solid tumors, human breast cancers exhibit very different clinico-pathologic characteristics and increasingly defined. HER2-positive breast cancer and improves overall survival [4]. There is, still an unmet clinical need to improve patient outcome in trastuzumab-treated BRC patients. The introduction of anti-angiogenic (AA) therapies represents a major advancement in treating human cancers. Despite favorable clinical trial results and several regulatory approvals (Table 1), majority of patients who initially respond to anti-angiogenic therapies eventually develop progressive disease [6]. De novo or acquired resistance to anti-angiogenic therapies is another major clinical challenge
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